Cross-Species analysis defines the conservation of anatomically-segregated VMH neuron populations

  1. Alison H Affinati
  2. Paul V Sabatini
  3. Cadence True
  4. Abigail J Tomlinson
  5. Melissa Kirigiti
  6. Sarah R Lindsley
  7. Chien Li
  8. David P Olsen
  9. Paul Kievit
  10. Alan C Rupp
  11. Martin G Myers Jr  Is a corresponding author
  1. University of Michigan, United States
  2. Oregon National Primate Research Center, United States
  3. Novo Nordisk Research Center, United States

Abstract

The ventromedial hypothalamic nucleus (VMH) controls diverse behaviors and physiologic functions, suggesting the existence of multiple VMH neural subtypes with distinct functions. Combing Translating Ribosome Affinity Purification with RNA sequencing (TRAP-seq) data with snRNA-seq data, we identified 24 mouse VMH neuron clusters. Further analysis, including snRNA-seq data from macaque tissue, defined a more tractable VMH parceling scheme consisting of 6 major genetically- and anatomically-differentiated VMH neuron classes with good cross-species conservation. In addition to two major ventrolateral classes, we identified three distinct classes of dorsomedial VMH neurons. Consistent with previously-suggested unique roles for leptin receptor (Lepr)-expressing VMH neurons, Lepr expression marked a single dorsomedial class. We also identified a class of glutamatergic VMH neurons that resides in the tuberal region, anterolateral to the neuroanatomical core of the VMH. This atlas of conserved VMH neuron populations provides an unbiased starting point for the analysis of VMH circuitry and function.

Data availability

Sequencing data have been deposited in GEO under accession code GSE172207

The following data sets were generated

Article and author information

Author details

  1. Alison H Affinati

    Internal Medicine, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  2. Paul V Sabatini

    Internal Medicine, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6613-566X
  3. Cadence True

    Oregon National Primate Research Center, Beaverton, United States
    Competing interests
    No competing interests declared.
  4. Abigail J Tomlinson

    Internal Medicine, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  5. Melissa Kirigiti

    Oregon National Primate Research Center, Beaverton, United States
    Competing interests
    No competing interests declared.
  6. Sarah R Lindsley

    Oregon National Primate Research Center, Beaverton, United States
    Competing interests
    No competing interests declared.
  7. Chien Li

    Obesity, Novo Nordisk Research Center, Seattle, United States
    Competing interests
    Chien Li, is an employee of Novo Nordisk A/S.
  8. David P Olsen

    Internal Medicine, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  9. Paul Kievit

    Oregon National Primate Research Center, Beaverton, United States
    Competing interests
    No competing interests declared.
  10. Alan C Rupp

    Internal Medicine, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5363-4494
  11. Martin G Myers Jr

    Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United States
    For correspondence
    mgmyers@umich.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9468-2046

Funding

National Institutes of Health (dk056731)

  • Martin G Myers Jr

Novo Nordisk

  • Martin G Myers Jr

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mice used in this study were maintained in accordance with University of Michigan Institutional Animal Care and Use Committee (IACUC), Association for the Assessment and Approval of Laboratory Animal Care (AAALAC) and National Institutes of Health (NIH) guidelines under protocol number PRO00007438 (PI Myers).Nonhuman primate tissue was obtained post-mortem from the Tissue Distribution Program at ONPRC. Animal care is in accordance with the recommendations described in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and animal facilities at the Oregon National Primate Research Center (ONPRC) are accredited by the American Association for Accreditation of Laboratory Animal Care International. ONPRC does not provide protocol numbers for security reasons.

Reviewing Editor

  1. Ana Domingos, University of Oxford, United Kingdom

Publication history

  1. Received: April 2, 2021
  2. Accepted: May 14, 2021
  3. Accepted Manuscript published: May 21, 2021 (version 1)
  4. Accepted Manuscript updated: May 24, 2021 (version 2)
  5. Version of Record published: June 7, 2021 (version 3)

Copyright

© 2021, Affinati et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alison H Affinati
  2. Paul V Sabatini
  3. Cadence True
  4. Abigail J Tomlinson
  5. Melissa Kirigiti
  6. Sarah R Lindsley
  7. Chien Li
  8. David P Olsen
  9. Paul Kievit
  10. Alan C Rupp
  11. Martin G Myers Jr
(2021)
Cross-Species analysis defines the conservation of anatomically-segregated VMH neuron populations
eLife 10:e69065.
https://doi.org/10.7554/eLife.69065

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